Disease/Drug of interest: Influenza Virus


Motivation and Background:

Commonly known as "the flu", Influenza is an infectious disease caused by the influenza virus. A person will experience symptoms of the flu a couple days after being exposed to the virus. Common symptoms include: a high fever, runny nose, sore throat, muscle pains, headache, coughing, and fatigue. There are four types of influenza viruses: A, B, C and D. Human influenza A and B viruses cause seasonal outbreaks of the disease during the winter months in the United States. Influenza type C infections generally cause a mild respiratory illness. Influenza D viruses affect cattle and are not known to cause illness in humans [1].

The Influenza A viruses are divided into two types based on the two proteins on the surface of the virus: the hemagglutinin and the neuraminidase. With in that, there are 18 different hemagglutinin types and 11 different neuraminidase types [1].

Influenza A viruses is further broken down into different strains. The types of influenza A viruses found in people are H1N1 and H3N2. In recent history, a new influenza A (H1N1) virus (CDC 2009 H1N1 Flu website) emerged to cause illness in people. This virus was very different from the human influenza A (H1N1) viruses circulating at that time. This new virus caused the first influenza pandemic in more than 40 years. That virus (often called “2009 H1N1 ” or “Swine Flu”) has now replaced the H1N1 virus that was previously circulating in humans. Unlike Influenza A viruses, Influenza B viruses do not have types but only have strains. Currently circulating influenza B viruses have two lines, B/Yamagata and B/Victoria [1].
VDS1.png
Fig. 1 ~100,000x magnified view of the Influenza Virus

Influenza A (H1N1), A (H3N2), and one or both influenza B virus strains are included in each year’s influenza vaccine. The seasonal flu vaccine does not protect against influenza C viruses. In addition, flu vaccines do not protect against illnesses caused by other viruses that also can cause influenza-like symptoms. There are many other non-flu viruses that can result in illnesses similar to influenza that spread during the winter season [1].

In the last century there have been four major flu pandemics. All four pandemics were caused by different types of influenza viruses that had been introduced to humans from animals. This is why scientists are constantly on the keeping an eye out for any new flu viruses that might be able to infect humans and cause high levels of illness or death. Even if the virus is not particularly lethal, high numbers of people off sick from work or school can have serious effects on the various aspects of life such as education, careers and the economy.

Around the world, hundreds of millions of people are infected with the influenza virus each year, and more than 100,000 people die from the virus. The influenza vaccine is useful, but it has to be changed and updated almost every year to keep up with the evolution of the flu virus. Understanding how and when the virus is likely to change is important in order to maintain good levels of public health.

References:
[1] Center for Disease Control. Types of Influenza Viruses https://www.cdc.gov/flu/about/viruses/types.htm (accessed Feb 5, 2017).
[2] Oseltamivir (By mouth) - National Library of Medicine - PubMed Health https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011518/?report=details#side_effects (accessed Feb 5, 2017).
[3] National Center for Biotechnology Information. PubChem Compound Database; CID=65028, https://pubchem.ncbi.nlm.nih.gov/compound/65028 (accessed Feb. 6, 2017).
[4] A Bioequivalence Study of Oseltamivir From Oseltamivir 75 mg Caps (Pharmacare PLC, Palestine) and Tamiflu® 75 mg Caps (Hoffmann-La Roche, Switzerland) https://clinicaltrials.gov/ct2/show/study/NCT02507648?term=tamiflu&rank=1 (accessed Feb 5, 2017).

External links:

https://www.cdc.gov/flu/about/viruses/types.htm
https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011518/?report=details#side_effects
https://pubchem.ncbi.nlm.nih.gov/compound/65028
https://clinicaltrials.gov/ct2/show/study/NCT02507648?term=tamiflu&rank=1
https://pandorareport.org/tag/tamiflu/

Target Information:

Viral Neuraminidase

Size: molecular weight of the protein

The molecular mass of the monomer is ≈ 60 kDa, and ≈ 240 kDa for the tetramer (one viral particle has approximately 50 tetramers).

Location:

Viral neuraminidase is a type of neuraminidase found on the exterior of the influenza virus.

Function in a normal cell:

Viral neuraminidase allows the virus to be released from the host cell. Neuraminidases are enzymes that separate the sialic acid groups from glycoproteins which aids the virus in replication.

Drug Information: Oseltamivir

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Fig. 2 Two-dimensional figure of the chemical make up of the drug used to inhibit the influenza virus, Oseltamivir.

Schematic figure of drug: Unable to find
Formula: C16H28N2O4
Molecular weight: 312.41 g/mol
CAS Number: 204255-11-8
Delivery method: Capsule, Liquid
Side effects: Nausea, vomiting, diarrhea, stomach pain, or upset stomach [2]
Allergic Reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth or throat, chest tightness, trouble breathing, blistering, peeling, red skin rash, confusion, agitation, seeing or hearing things that are not there, change in mood or behavior, seizures, fever, chills, cough, sore throat, or body aches
Other names: TamiFlu [3]
Maker or company: Hoffmann-La Roche Inc.
Is it patented? Yes-13 Patens
Clinical Trials: 113 [4]
Origin: Shikimic acid
Alternatives to this drug: Zanamivir (Relenza)
Other uses: No
VDS3.jpgFig. 3 Commercial package of the drug, Oseltamivir (TamiFlu) shown in capsule form.